Personal Chemistry

Until 2004, Biotage (formerly Personal Chemistry) offered the Emrys monomode reactor series of instruments (Fig. 3.19). Although no longer commercially available, many instruments are currently still in use. Therefore, this line of products is discussed in detail in this chapter [15]. 

Fig. 3.19 Personal Chemistry (Biotage) Emrys product series Creator,...

A very useful tool is the Emrys Knowledge Database, representing a collection of detailed protocols for reactions performed with Biotage (Personal Chemistry) instmments. To date, this web-based tool contains around 4000 entries. 

Monomode reactors Prolabo, Synfhe-wave S402 and S1000 (actually not on the market). CEM, STAR system 2 and 6 and Discover. Personal Chemistry, Smith Synthesizer and Smith Creator. Temperature measurement is one of the main problems in microwave-assisted reactions. See Ref. [2] for temperature-measurement systems. 

These reactions have been performed using a Personal Chemistry Smith Synthesizer. 

We thank Mr Gunnar Wikman and Dr Peter Nilsson for help with the manuscript. We also thank the Swedish Research Council and Knut and Alice Wallenberg Foundation. We acknowledge Personal Chemistry (now Biotage AB) for provision of the Smith Synthesizer. 

A further development of the Mannich reaction is the boronic Mannich reaction, which has been described extensively by Petasis and co-workers under conventional heating methods. Gupta et al. (Personal Chemistry, Uppsala, Sweden, internal report) have performed this reaction under microwave condition in acetonitrile (Scheme 5.11). A reaction time of 4 min at 120° C afforded the products in yields ranging from 25 to 100%. Alternative amines and boronic acids could be used, but the glyoxylic acid was essential for product formation. The major drawback with this reaction under microwave conditions at present is that the outcome is highly substrate dependent. 

Aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]-quinazolines Isatoic anhydride could also be reacted with amino-, hydroxyl- or thiolanilines to form 2-(2-aminophenyl)benz-imidazoles, oxazoles or thiazoles, Scheme 5.38. In the case of 2-(2-aminophenyl)benzimidazoles (X=N), the product was formed after 3 min at 150°C in acetic acid. The products could subsequently be further elaborated 6-aryl-5,6-dihydrobenzo[4,5]imidazo[l,2-C]quinazolines, a four ring system, was formed by treatment of the 2-(2-aminophenyl) benzimidazole (X=N) with different aldehydes in acetic acid at 150°C for 5 min (J. Westman, and K. Orrling, Personal Chemistry, Uppsala, Sweden, unpublished results). Fifteen compounds were synthesised in 20-75% overall yield. This 3 + 5 min procedure should be compared to the conventional heating protocol developed by Devi and co-workers57, where each reaction step was run overnight to eventually afford the products in only 30-50% yield. 

At this time, we had access to a microwave system from Personal Chemistry called the Smith Synthesizer (Personal Chemistry AB, Uppsala, Sweden) and so we attempted this difficult cycloaddition reaction13. As evident in Table 8.1, the results with the microwave were remarkably improved compared to the conventionally heated counterpart. The product yield and purity was substantially higher than what was observed in the pressure tubes. With this first positive example, we were encouraged to try systems that had not been able to produce an observable product in the pressure tubes. The condensation of a fused cyclohexyl maleimide had not produced any product in our previous efforts, but with microwave heating for a short 5 min reaction time at 180°C we were able to isolate a satisfactory amount of the desired product. 

Combinatorial chemistry has moved from specially centralized laboratories, often equipped with multimillion-dollar robots, onto the bench of individual medicinal chemists. This change in direction requires the availability of personal chemistry tools that are simple to operate, easy to arrange in the laboratory, and reasonably priced. Such instruments are now available for the effective synthesis of combinatorial libraries. The Encore synthesizer represents a simple and efficient personal chemistry tool that allows the execution of directed split-and-pool combinatorial synthesis. The current version of the Encore synthesizer is designed for solid-phase synthesis on SynPhase Lanterns however, it can be modified for synthesis on alternative solid supports such as resin plugs from Polymer Laboratories (e.g., StratoSpheres Plugs). 

Fig. 4. Monomode microwave reactor with integrated robotic platform for automated use (left). A liquid handler allows dispensing of reagents into Teflon-sealed reaction vials, while a gripper moves each vial in and out of the microwave cavity after irradiation. The instrument processes up to 120 reactions per run with a maximum throughput of 12-15 reactions/h. The temperature is measured by an IR sensor on the outside of the reaction vessel. Details of the cavity/gripper (top right) and reaction vials (bottom right) are also displayed (Emrys Synthesizer, Personal Chemistry AB). Reprinted with permission from Wiley-VCH.41 (See color insert.)...

Fig. 1. Personal Chemistry Smith synthesizer. (Photograph compliments of Personal Chemistry Inc.) (See color insert.)...

Resin 4 (R1 = CH3) (50 mg, 0.014 mmol) was weighed into a conical Personal Chemistry Smith process vial equipped with a conical-shaped stir bar. To the resin was added 4-fluorophenylboronic acid (11 mg, 0.08 mmol), DMF (1 ml), 2 M aqueous sodium carbonate (80 pi), and di-chlorobis(triphenylphosphine)palladium(II) (1-2 mg). The heavy walled glass vial was crimp sealed and placed on the Gilson platform. The micro-wave program was set to a 5 min duration at 180° on the normal absorption setting and the vial was then processed. After completion, the vial was decrimped and resin 5 (R1 — CH3, R2 = 4-F-phenyl) was transferred to a fritted tube and washed with DMF, H20, MeOH, and DCM (3x each). 

I began this article with a single experiment of my own and was led to discuss in my essay, some results which I cannot count as my own personal chemistry. My fictitious interviewer may now ask Is that your whole story, or is there anything else of some importance omitted, and in what field are you still active now ... 

Acknowledgements Parts of author s work were supported by National Institutes of General Medical Sciences SBIR Grants (2R44GM062717-02 and 2R44GM067326-02). The Pd-catalyzed microwave reactions were conducted under license to US patent 6,136,157 and European patent No. 0901453 held by Personal Chemistry, now Biotage. 

Equipment vendors include Prolabo Co., France Personal Chemistry Ltd., Cambridge, England Milestone Inc., Monroe, Connecticut, USA and CEM Microwave Technology, Matthews, North Carolina, USA. 

When the chemistry department was established in 1977, there were 24 majors from the first year to senior level. The course offerings on campus at that time were limited to the general chemistry, organic chemistry, and biochemistry courses. That year, in 1977, three students graduated with a degree in chemistry. The department had a three-person chemistry faculty. 

Personal Chemistry, Inc. (Biotage), unpublished data. Available through www.biotagepathhnder.com. 

The three case studies described herein consist of unpuhhshed data from Personal Chemistry, Inc. (Biotage). The reaction conditions for individual steps are avaUahle from www.biotagepathfinder.com... 

These data were supplied by Biotage (previously Personal Chemistry) Kunsgaten 76,SE-753 18 Uppsala,Sweden. similar data are available from the other manufacturers listed below. 

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